Gp41 antigens

Abstract

The present invention deals with a modified polypeptide comprising three contiguous segments N, L and C represented by the formula N-L-C and comprising: a N-helix region of gp41 (N), a C-helix region of gp41 (C), and a connecting loop comprising a synthetic linker (L) between the N and C-helices, the linker replacing amino acids 593-617 of gp41, the numbering scheme being based upon the prototypic isolate HIV-1 HxB2 Clade B strain, said polypeptide comprising the calveolin-1 neutralizing and 98.6 D epitopes, but not 2F5 and 4E10 epitopes, not the fusion peptide, the polypeptide having a minimal immunogenic cross-reactivity with human interleukin 2 (IL2).

The invention claimed is: 
     
       1. A modified human immunodeficiency virus type 1 (HIV-1) gp41 polypeptide consisting of a full-length sequence set forth in SEQ ID NOS: 18-20. 
     
     
       2. The polypeptide according to  claim 1 , wherein the polypeptide consists of the full-length sequence set forth in SEQ ID NO: 18. 
     
     
       3. The polypeptide according to  claim 1 , wherein the polypeptide consists of the full-length sequence set forth in SEQ ID NO: 19 or 20. 
     
     
       4. An aqueous composition comprising a polypeptide according to  claim 1 , said polypeptide forming a trimer in an aqueous medium. 
     
     
       5. An aqueous composition according to  claim 4 , wherein said trimer is stable. 
     
     
       6. A conjugate comprising a polypeptide according to  claim 1 , conjugated with a virosome. 
     
     
       7. A polynucleotide encoding a polypeptide according to  claim 1 . 
     
     
       8. A polynucleotide according to  claim 7 , wherein the polynucleotide comprises the full-length sequence set forth in SEQ ID NO: 21 or 28. 
     
     
       9. A polypeptide encoded by a polynucleotide according to  claim 7 . 
     
     
       10. A trimer comprising three polypeptides as defined in  claim 1 . 
     
     
       11. An expression vector comprising at least a transcription promoter, a polynucleotide according to  claim 7  and a transcription terminator. 
     
     
       12. An isolated host cell comprising an expression vector according to  claim 11 . 
     
     
       13. An antigenic or immunogenic composition comprising: a polypeptide according to  claim 1 ; a conjugate comprising the polypeptide conjugated with a virosome; or a trimer comprising three of the polypeptides. 
     
     
       14. A pharmaceutical preparation comprising: a polypeptide according to  claim 1 ; a conjugate comprising the polypeptide conjugated with a virosome; a trimer comprising three of the polypeptides; or an expression vector comprising at least a transcription promoter, a polynucleotide encoding the polypeptide, and a transcription terminator. 
     
     
       15. A pharmaceutical preparation according to  claim 14  configured for use in immunotherapy. 
     
     
       16. A medicament configured to induce an adaptative immune response and/or an innate immune response directed against a gp41 protein of a human immunodeficiency virus, the medicament comprising: a polypeptide according to a  claim 1 ; a conjugate comprising the polypeptide conjugated with a virosome; a trimer comprising three of the polypeptides; or an expression vector comprising at least a transcription promoter, a polynucleotide encoding the polypeptide, and a transcription terminator. 
     
     
       17. A method for inducing an immune response in a patient, comprising at least a step of administrating to an individual in need thereof an effective amount of the polypeptide according to  claim 1 , a conjugate comprising the polypeptide conjugated with a virosome, or a trimer comprising three of the polypeptides. 
     
     
       18. The method according to  claim 17 , wherein said effective amount is administered systematically by injection and/or topically by the mucosal route. 
     
     
       19. The method according to  claims 18 , wherein said mucosal route is chosen from genito-urinary tract, gastro-intestinal tract, anorectal route, respiratory tract, upper mucosal tissue, mouth-nasal route and combinations thereof.